What my Illness Taught Me About Health

(The Role of the Immunoglobulins)

Allen R. Dyer, M.D., Ph.D.dyer@etsu.edu

http://faculty.etsu.edu/dyer

Charles Janeway, M.D.Father of Clinical immunology

• Pediatrician-in-chief at Boston Children’s Hospital for 30 years

• Described “A gamma globulin emia”

in children susceptible to infections

Patient: ARD

• Aug, 1997 - First symptoms: chin numbness• Jan, 1998 - Rib tenderness• March, 1998 - diagnosis: Multiple Myeloma• March - June: 3 rounds of low-dose chemo • July-Sept: Bone Marrow Transplant

Differential Diagnosis of Chin numbness/pain

• Multiple sclerosis• Brain tumor• Trigeminal neuralgia• Herpes zoster• Infection - neuritis• Infection - systemic• Cancer• Functional • Zebras

The law of parsimonyPar’si-mo’ny -

Unusual or excessive frugality. Adoption of the simplest assumption in the

interpretation of data

Investigative FindingsSerum immunofixation revealed an IgA-kappa monoclonal gammopathy.

Bone x-rays revealed radiolucent lesions within the skull, ribs, clavicles, right ischium, and right mid-humerus. The left 5th rib was fractured.

A bone marrow biopsy showed a slight increase in overall cellularity (70%)

A fine needle aspirate of the left 7th rib revealed in-filtration with atypical plasma cells.

Acquired immunodeficiencies

Genetics

Cancer is a genetic illness:It is not necessarily a hereditary illness.

Laboratory ResultsCBC Mild normochromic, normo-

cytic anemia (H/H 11, 34)Erythrocyte sedimentation rate Markedly elevated

(107mm/hr)Serum biochemistries Mildly elevated calcium

(10.3 mg/dL)Serum protein electrophoresisSPEP

Mild polyclonal elevation in gamma globulin (2.3 grm/dL)

Quantitative immunoglobulins IgA hypergammma-globulinemia (1,880 mg/dL)

Immunofixation Monoclonal IgA-kappa paraprotein

Lab results (cont.)

Serum interleukin -6 Absent

Urine protein electro-phoresis (UPEP)

No protein in urine! ☺

Myeloma Staging SystemCreatinine Level STAG

EMedian Survival

A<2mg/dL IA 61 months

B>2mg/dL IIA,B 55 months

III 15 months

ß-2 microglobulin

<0.004gm/L I 43 months

>0.004gm/L II 12 months

Myelomatosis involving the skull

Glass, D. A. et. al. N Engl J Med December 25, 2003

Formation of Osteolytic Lesionsin Multiple Myeloma

Myeloma cells secrete at least two molecules that modulate the bone microenvironmentin a manner favorable to tumor growth. Receptor activator of nuclear factor k-B ligand(RANKL) acts to stimulate osteoclast formation andactivity leading to bone erosion, whereas dickkopf1 (DKK1) appears to inhibitosteoblasts, thus preventing repair of the lesions.

Pathogenesis and Clinical ManifestationsClinical finding Underlying Cause Pathogenic Mech

Hypercalcemia,Fractures, pain

Skeletal destruction OsteoclastActivating Factors

Renal failure Light chain proteinuria

Tumor products: OAF, DNA

Anemia ↓production↑destruction

Inhibitory factorsAutoantibodies

Infection Hypogamma-globulinemia

↓production↑IgG catabolism

Neurologic Sx Cord compression M globulins

Bleeding ↓clotting factors Tumor products

ANTICOAGULATION IN DEEP VEIN THROMUS

Risk of Clot/thrombus vs. Risk of Bleed

Rule vs. Therapeutic principle

Complicating factors- Cancer- Steroids- Impending surgery- ? Underlying coagulation disorder

Playing the oddsInformed consent: 1998

1-3 % change of death from treatment(down from 10-15 %)

30% chance of complete cure---

Duke Myeloma protocol: 1997-2002n = 85

40 % still living3 doing well

Charles (“Charlie”) Janeway, Jr. 1943-2003“Father of Innate Immunity”

“How the Body Recognizes Foreign Invaders”

Factors involved in Healing• 1. Education - accurate information• 2. Positive attitude• 3. Reducing stress

• Relaxation• Exercise• Diet

• 4. Eliminating Negative Beliefs and Emotion• Eliminate Anger, Rage, Fear, Guilt• Forgiveness• Problem Solving• Goal setting - creating positive future goals

• 5. Positive visual imagery - commands and instructions to the body

Lance Armstrong Allen Dyer

1998 - age 52diagnosed with MM

2005 - age 602nd Tour de France

Ascention of Mt. Ventoux

1996 - age 25 -diagnosed with Testicular cancer

(metastases to stomach, lungs, brain)

2005 - age 34 -wins 7th Tour de France

Possible explanatory factors• CHEMOTHERAPY• Attitude Community• Spirituality Love/Family support• Prayer - Meditation

• Mind over matter Mountain climbing• Environment Hanging out with Buddhists

EXERCISE FUN• Diet Genes Laughter

Explanatory factors (cont.)

Luck

Good Fortune Blessing

RandomnessIndeterminacy

Exercise and Cancer• Exercise improves immune function,

lymph flow, and detoxification• Helps regulate blood sugar levels• Relieves both depression and anxiety• Physical activity has also been shown to

improve tolerance to chemotherapy. • Fitness level prior to treatment helps

endure the rigors of treatment.

Healthy behaviors(less smoking,

drinking)

Social support(faith, communities,

marriage)

Positive emotionshope/optimism

(less stress, anxiety)

Religious involvement

Health(less immune

suppression, stress hormones, and suicide)

So What?

• Social capital operates through psychological and biological processes to improve individuals’lives.

• People whose lives are rich in social capital cope better with traumas and fight illness more effectively.

Psycho Neuro Immunology PNI

• The study of the link between psychological states and the functioning of the nervous system.

• The study of the interactions among the mind, immune system, and the neurological system that modulate susceptibility to disease or its progression

In the Wake of the Tsunami• PsychoSocial Care of Disaster Victims

Tsunami Survivors

Factors involved in healing• CHEMOTHERAPY• Attitude Community• Spirituality Love/Family support• Prayer - Meditation

• Mind over matter Mountain climbing• Environment Hanging out with Buddhists

EXERCISE FUN• Diet Genes Laughter

Stress and the Immune System

Stressor EventsCataclysmic Disaster

– Effecting multiple people at the same time• Earthquake,

war, terrorismPost-traumatic

- Re-experience of stress event as a dream or flashback

War experienceChildhood abuse

Personal– Major life event that

have immediate effect but fade with time

Background– Daily irritating events

UpliftingPositive events that make one feel good

Non-pharmacologic approach to anxiety

• Deep breathing• Progressive muscle relaxation• Guided imagery

“Milt, I’m beginning to think that your illnessis a disharmony of life energy”